The major emphasis of the current investigations focuses on the cellular requirements for human T lymphocyte colony formation and the means of perturbing the activities of the different cellular elements. Mononuclear cells, when plated in agar along with PHA, undergo proliferative expansion leading to the formation of discrete colonies. Following separation of these cells on Sephadex G10 columns, the nonadherent fraction (greater than 92% T cells) is incapable of clonal expansion. However, growth can be restored by coculturing these T cells with adherent cells or tumor cells of either monocytic (U937, HL60) or B-lymphocytic (Raji, Daudi) lineages. Soluble factors derived from these cells can also restore growth potential. These studies will be extended to evaluate the following: (1)\isolating and characterizing stimulatory factors; (2)\defining the relationships between these and IL-1 and IL-2; (3)\examining the activities of phorbol esters; (4)\measuring the clonal responses of thymocytes; (5)\assessing the effects of several immunoregulatory drugs; (6)\evaluating the growth potential of T-cell subsets; and (7)\measuring colony-forming activities in patients with immunologically related disorders. A second major series of experiments are aimed at defining the therapeutic potentials of a combination of cyclophosphamide and methyl PGE1 in MRL/1 mice (an animal model of SLE).